Christian Pradier

Evaluating counseling outcome on adherence to prophylaxis and follow-up after sexual HIV-risk exposure: a randomized controlled trial

Abstract Objective. Post-exposure prophylaxis (PEP) is recommended for the management of sexual HIV-risk exposure. However, a high percentage of exposed patients discontinue both their 28-day prophylaxis course before 15 days and HIV testing follow-up before M3. The objective of this study is to assess the efficacy of a counseling intervention in enhancing both adherence to PEP and HIV testing follow-up. Methods. Between 1 June 2004 and 31 December 2005, 54 patients exposed to sexual HIV-risk exposure were included in a multicenter, prospective, controlled, randomized trial, comparing a group receiving a counseling intervention in addition to traditional medical management (intervention group (IG), n=28) vs. a control group (CG, n=26). Patients in the IG received interactive counseling interventions focused on adherence to PEP and to HIV testing follow-up, led by specially trained nurses. The main outcome measures were proportion of patients achieving 100% adherence to PEP as evaluated on D15 by a self-completed patient questionnaire and on HIV testing on D45 and M3. Results. Groups were well balanced at baseline for age, sex, and circumstances of exposure. The proportion of 100% adherent patients to PEP was significantly higher in the IG compared to the CG (54% vs. 23%, p=0.036). Patients in the IG were more likely to complete the HIV testing follow-up at D45 (86% vs. 54%, p=0.023) and M3 (68% vs. 38%, p=0.056). Conclusions. This study suggests the effectiveness of a counseling program to enhance adherence to both PEP and HIV testing follow-up after sexual exposure.

Relevance of lipopolysaccharide levels in HIV-associated neurocognitive impairment: the Neuradapt study

Contributory factors to HIV-associated neurocognitive disorders (HAND) have been shown to include age, co-morbid infections, medication toxicity, virological, genetic and vascular mechanisms, as well as microbial translocation of lipopolysaccharide (LPS), which is suspected to trigger monocyte activation and increase trafficking of infected cells into the brain. In this study, our aim was to assess the degree of neurocognitive impairment in a group of randomly selected HIV-infected patients and investigate potential risk factors, including LPS plasma levels. Furthermore, we evaluated the relevance of LPS as a potential marker for screening patients with mild neurocognitive impairment. LPS plasma levels were compared among patients with HAND and those with no HAND. As LPS has also been shown to be elevated in hepatitis C co-infection, the analysis was stratified according to the presence or not of hepatitis C virus (HCV) co-infection. Differences between groups were evaluated using chi-square tests and Kruskal–Wallis non-parametric tests. Stepwise logistic regression was performed to identify independent risk factors for HAND in the subgroups of HCV-positive and negative patients. A p value <0.05 was considered significant. Analyses were conducted using SPSS® software. From December 2007 to July 2009, 179 patients were tested (mean age 44, 73xa0% male, 87xa0% on treatment, 30xa0% HCV co-infected, median CD4 504/ml and 67xa0% with viral load below 40 copies/ml). HAND was identified in 40/179 patients (22xa0%), the majority displaying asymptomatic neurocognitive impairment or mild neurocognitive disorder. Univariate analysis showed that age, illicit drug use, hepatitis C co-infection, prior AIDS-defining events, CD4/CD8 ratio and LPS plasma levels were significantly associated with HAND. The median LPS level was 98.2xa0pg/ml in the non-HAND group versus 116.1xa0pg/ml in the HAND group (pu2009<u20090.014). No differences were found in LPS values between subgroups of impairment. There was a clear association between LPS levels and HAND in the HCV-positive group (pu2009=u20090.036), while there was none in the HCV-negative group (pu2009=u20090.502). No difference in degree of hepatic fibrosis was found between the HAND and non-HAND groups. In conclusion, LPS levels were associated with HAND in the HCV-positive group, while, in the HCV-negative group, age and pro-viral DNA were the only variables independently associated with HAND. There was no difference in degree of liver disease as predicted by score of fibrosis between HAND and non-HAND groups. The role of HCV co-infection and higher LPS levels in the pathogenesis of HAND in patients with viral suppression on treatment requires further investigation.

Incidence of inflammatory bowel disease in Corsica from 2002 to 2003.

OBJECTIVESnThe aim of this prospective epidemiological study was to determine the incidence of inflammatory bowel diseases (IBD) in Corsica using the same methodology as that of the EPIMAD registry.nnnMETHODSnBetween January 1st, 2002 and December 31, 2003, all gastroenterologists in Corsica (N=19) enrolled patients consulting for the first time with clinical symptoms compatible with IBD. Each case was reviewed by another expert gastroenterologist to assign a diagnosis of definite, probable, possible Crohns disease (CD), ulcerative colitis (UC) or unclassified/able chronic colitis.nnnRESULTnEighty-one new cases were recorded, including seventy-one diagnoses of IBD (definite and probable cases), with 20 (28%) CD, 49 (69%) UC and 2 (3%) unclassifiable chronic colitis. The age-adjusted incidence (per 105 inhabitants/year) was 4.05 for CD and 9.5 for UC. The female/male ratio and median age at time of diagnosis were 1.3 and 29 years for CD and 0.63 and 44 years for UC, respectively. The median time from symptom onset to diagnosis was five months for both diseases.nnnCONCLUSIONnIn Corsica, the observed incidence of CD is close to that observed in other metropolitan French regions. These data are contrary to the north-south gradient reported for this disease. Our figure of 9.5/10(5) for UC in Corsica is two-fold higher than reported in other metropolitan French regions. Genetic and/or environmental factors may explain these findings.

The mini mental state examination at the time of Alzheimer's disease and related disorders diagnosis, according to age, education, gender and place of residence: a cross-sectional study among the French National Alzheimer database.

The aim of this study was firstly to describe the MMSE (Mini-Mental State Examination) score upon initial diagnosis of Alzheimers disease and related disorders among the French population, according to age. Secondly, education, gender and place of residence were studied as factors potentially associated with delayed Alzheimers disease diagnosis. Design we conducted a cross sectional analysis of the French National Alzheimer database (BNA). Data from 2008 to 2012 were extracted. Patients were selected at the moment of their first diagnosis of AD (nu200a=u200a39,451). Results The MMSE score at initial diagnosis dropped significantly with increasing age. The test score increased with the degree of educational background regardless of age. Gender and place of residence were significantly related to the MMSE score, women and persons living in medical institutions having lower MMSE scores under the age of 90 years and at all educational levels. Conclusions Health care professionals should be aware of these risk factors in order to maximize chances of earliest possible diagnosis of Alzheimers disease and related disorders.

Virologically suppressed patients with asymptomatic and symptomatic HIV‐associated neurocognitive disorders do not display the same pattern of immune activation

Inversion of the CD4:CD8 ratio is a marker of immune activation and age‐associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV‐infected patients and explored differences according to clinical severity.

HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Disorders (HAND)

Background HIV-associated neurocognitive disorders (HAND) persist in the post-HAART era, characterized by asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorders (MND). High mobility group box 1 (HMGB1) is a non-histone chromosomal protein widely expressed in the nucleus of all eukaryotic cells, including brain cells, which acts as a potent proinflammatory cytokine when actively secreted from immune cells. Recent reports suggested that HMGB1 acts on microglial cells to promote neuroinflammation. In this study, our aim was to determine whether HMGB1 is involved in HAND, but also to identify early new markers of neurological impairment in HIV-infected patients. Methods CSF and serum were collected from 103 HIV-1-infected patients enrolled in Neuradapt, a prospective study of the prevalence of HAND in HIV-1 infected patients at Nice University Hospital. Stored fluids were assessed for immunological, virological, and brain metabolite parameters. In addition to HIV RNA and DNA measurements, expression of T-cell surface markers of activation (CD38 and HLA-DR) was analyzed on whole blood. Concentration of 27 cytokines and chemokines was measured using multiplex bead assays on serum and CSF. Concentration of HMGB1 and anti-HMGB1 IgG autoantibodies were also measured on the same samples. Changes in cerebral metabolites N-acetyl aspartate (NAA), Choline (Cho) and creatinine (Cr) were assessed by magnetic resonance microscopy (MRS). Results Clinical, virological and immunological characteristics were comparable between HAND (n = 30) and no HAND (n = 73) patients, except the absolute numbers of CD8+ T cells, which were higher in patients with HAND. Among the 29 molecules tested, only 4 of them were significantly upregulated in the CSF from HAND patients as compared to healthy donors i.e. HMGB1, anti-HMGB1 IgG antibodies, IP-10 and MCP1. CSF HMGB1 levels were positively correlated with HIV-1 DNA in aviremic HAND patients, suggesting a positive impact of HMGB1 on HIV reservoirs. Moreover, in contrast to NAA/Cr and Cho/NAA ratios, circulating anti-HMGB1 IgG antibody levels could discriminate patients with no HAND from patients with no HAND and a single deficit (average ROC-AUC = 0.744, p = 0.03 for viremic patients), thus enabling the identification of a very early stage of neurocognitive impairment, Conclusion We report that brain injury in chronically HIV-infected patients on stable HAART is strongly associated with persistent CNS inflammation, which is correlated with increased levels of HMGB1 and anti-HMGB1 IgG in the CSF. Moreover, we identified circulating anti-HMGB1 IgG as a very early biomarker of neurological impairment in patients without HAND. These results might have important implication for the identification of patients who are at high risk of developing neurological disorders.

A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication

Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2xa0years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45xa0%). The majority of HAND cases consisted of ANI (26xa0%) and MND (16xa0%). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, pxa0=xa00.003) and CD4/CD8 decrease more frequent (60 vs 31xa0%, pxa0=xa00.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.

Taux observés des CIN en 2006 avant la vaccination anti-HPV parmi les résidentes des Alpes-Maritimes

OBJECTIVEnThe incidence rate of uterix cervical cancer in 2006 in the Alpes-Maritime was 6.2 per 100,000 women. The existence of curable precancerous lesions and an effective vaccine make it a target cancer in public health. The objective of this study was to establish prevalence of cervical intraepithelial neoplasia in 2006 before the campaign of vaccination against HPV.nnnPATIENTS AND METHODSnRetrospective study including all histological samples (smears excluded) of the cervix, performed in 2006 with a diagnosis of intraepithelial Neoplasia among residents of the Alpes-Maritimes. Extraction codes corresponding was carried out by all pathology laboratories located in the Alpes-Maritimes and around. A comparison of codes with pathology reports was performed for 11.4% of random samples.nnnRESULTSnThis study included 2066 patients aged 16 to 88 years. The average age was 37.3 years (±12.3). Among these patients, most pejorative intraepithelial neoplasia lesion was CIN 1, CIN 2, CIN 3, respectively for 941, 380 and 375 patients. Prevalence of CIN 2 among women 20 to 25 years old was similar to rates seen in 35 to 39 years old (166.5 per 100,000) and the rate of CIN 3 was similar to that seen in 45 to 49 years (78.1 per 100,000).nnnDISCUSSION AND CONCLUSIONnRates of CIN for the entire female population of the Alpes-Maritimes in 2006 has been established. The results observed in women aged less than 25 years old will be useful for comparison after the campaign of vaccination against HPV.

“As du Coeur” study: a randomized controlled trial on physical activity maintenance in cardiovascular patients

BackgroundThe benefits of supervised physical activity programs in cardiac rehabilitation have been amply demonstrated, but the quantity of physical activity often declines quickly once supervision ends. This trial assesses the effectiveness of an experimental intervention drawing on habit formation theory to maintain physical activity.MethodsCardiovascular patients (Nu2009=u200947) were randomly assigned to one of two groups. The first group participated in two supervised physical activity (SPA) sessions per week for 20xa0weeks. The second group was offered a progressively autonomous physical activity (PAPA) program as follows: the same supervised program as the SPA group for 10xa0weeks and then a further 10xa0weeks with one supervised session replaced by a strategy to build and sustain the habit of autonomous physical activity. The International Physical Activity Questionnaire (IPAQ; Craig et al. Med Sci Sports Exerc 35(8):1381–1395, 2003) was used to measure the quantity of physical activity, which was the primary outcome. The number of participants was limited, and we thus took multiple IPAQ measurements (at 0, 5, 7, 9 and 12xa0months after the start of the intervention) and used a mixed model for analysis. Physical condition, automaticity of the physical activity behavior, motivation, and quality of life were examined for changes.ResultsNo significant between-group differences were noted for physical activity behaviors after the program, physical condition, motivation, or behavioral automaticity. The PAPA group nevertheless completed more PA sessions during the intervention, and their quality of life was significantly higher than that of the SPA group at 12xa0months.ConclusionAlthough the number of supervised sessions was lower, the progressively autonomous PA program resulted in the same or even higher positive outcomes than the fully supervised PA program.Trial registrationCurrent Controlled Trials ISRCTN77313697, retrospectively registered on 20 November 2015.

Protocol of the "As du Coeur" study: a randomized controlled trial on physical activity maintenance in cardiovascular patients

BackgroundAlthough the benefits of supervised physical activity programs in cardiac rehabilitation have been well documented, the amount of physical activity often drops quickly after the end of the supervised period. This trial (registered as ISRCTN77313697) will evaluate the effectiveness of an experimental intervention based on habit formation theory applied to physical activity maintenance.Methods/DesignCardiovascular patients (Nu2009=u200956) will be individually randomized into two groups. Two supervised physical activity (SPA) sessions per week will be offered to the first group for 20xa0weeks. Progressively autonomous physical activity (PAPA) will be offered to the second group as follows: 10xa0weeks of the same supervised program as the SPA group followed by 10 more weeks in which one supervised session will be replaced by a strategy to build and sustain the habit of autonomous practice of physical activity. The primary outcome is the amount of physical activity measured by the International Physical Activity Questionnaire (IPAQ; Craig et al., Med Sci Sport Exercises 35(8):1381–95, 2003). To compensate for the limited capacity to recruit subjects, multiple IPAQ measurements will be made (at T0, T5, T7, T9 and T12 months after the start of the intervention) and analyzed using the mixed model approach. We will also assess changes in physical and physiological indicators, automaticity of the physical activity behavior, motivation and quality of life. Last, we will assess the cost-effectiveness for each type of program.DiscussionIf proven to be effective, the PAPA intervention, which requires fewer supervised sessions, should provide a cost-effective solution to the problem of physical activity maintenance in cardiac rehabilitation.